NDT Advance Access originally published online on March 26, 2007
Nephrology Dialysis Transplantation 2007 22(7):2063-2067; doi:10.1093/ndt/gfm103
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Scleroderma-like acute renal crisis in a patient with scleromyxedema
1Division of Nephrology, Department of Internal Medicine, 2Department of Pathology, 3Division of Immunology, Department of Internal Medicine and 4Department of Dermatology, Medical School Hannover, Hannover, Germany
Correspondence and offprint requests to: Wilfried Gwinner, Department of Nephrology, Medical School Hannover Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Email: wgwinner{at}t-online.de
Keywords: acute renal failure; central nervous system disease; intravenons immunoglobulins; mucinosis; scleroderma; thrombotic microcangiopathy
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Introduction |
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Scleromyxedema is a rare connective tissue disorder, characterized by generalized skin induration with waxy yellow–red papules. Histological features include cutaneous mucin deposition in the superficial dermis, specifically hyaluronic acid, and fibroblast proliferation. Most patients with this disorder present with monoclonal paraproteinaemia, mainly IgG lambda. Oesophageal abnormalities with dysphagia, muscle weakness, dyspnoea with abnormal diffusing capacity, restrictive lung disease and cor pulmonale, pericardial effusions, central nervous system abnormalities and neuropathies, arthralgias and Raynaud's phenomenon have been observed, and may be associated with significant morbidity and mortality [1–3]. In post-mortem studies, interstitial and vascular mucin deposition in inner organs has been found inconsistently [2,4]. Renal disease is rare in patients with scleromyxedema. In this article, we report a middle-aged female with scleromyxedema and a scleroderma-like acute renal crisis.
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Case |
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A 48-year old female was admitted with dyspnoea at rest, increasing bilateral leg oedema and general weakness. In the weeks prior to admission, she had gained about 5 kg of weight and observed increasing dyspnoea on exertion and increasing induration of the skin of her face, trunk and limbs. Her past medical history was significant for facial photosensitivity since age 20 years. Because of a papular rash involving the face and limbs, a biopsy was performed 5 years prior to admission, establishing a diagnosis of scleromyxedema (Figure 1). At that time, the only abnormal immunological test was an ANA titer of 1:80, with a speckled fluorescence pattern and monoclonal IgG kappa protein. The patient was normotensive and had normal renal function without proteinuria or haematuria. She subsequently developed stiffness and swelling of the fingers, tenosynovitis of her wrist and peripheral neuropathy. Various therapeutic regimens, including oral prednisolone as monotherapy or in combination with cyclophosphamide, chloroquine and a trial of rituximab were of limited efficacy.
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On admission the patient had a blood pressure of 160/100 mmHg. She had extensive leg oedema. The skin of her face, trunk and limbs was indurated and showed papules measuring
3 mm in diameter, with a grayish-livid appearance. The oral orifice was small (Figure 2). Breath sounds were diminished at the base. Chest X-ray revealed large bilateral pleural effusions, which were transudative. An echocardiogram showed a pericardial effusion of 23 mm without haemodynamic compromise. The blood cell count showed leucocytes of 10 700/µl, 10% of those were lymphocytes, 10% monocytes, 70% granulocytes and 10% eosinophiles. Serum C-reactive protein was increased to 38 mg/l, and serum creatinine to 124 µmol. Serum protein was reduced to 48 g/l, with 21 g/l albumin and electrophoresis showed gamma globulins of 28% and 7 g/l myeloma protein. Other immunological and serological testing was non-contributory. The urinary sediment was active with red blood cell casts and 5–10 erythrocytes per HPF. Proteinuria was 650 mg per day.
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Oral prednisolone (100 mg/day) and an intravenous bolus of cyclophosphamide (total 915 mg, 500 mg/m2) were given empirically. Antihypertensive treatment was begun which decreased her blood pressure to values between 125/70 and 145/90 mmHg. Five days after admission, the patient developed a generalized seizure. Measurement of the blood pressure after cessation of the seizure revealed severe hypertension, with 215/130 mmHg. Before adequate antihypertensive therapy could be instituted, she developed respiratory failure requiring temporary mechanical ventilation. Head imaging with computed tomography and magnetic resonance and spinal fluid analysis were unrevealing. During the next 2 weeks, the blood pressure became increasingly difficult to control, with maximal values of 250/145 mmHg, despite treatment with ACE-inhibitor, ß-Blocker, calcium channel blocker, clonidine, diuretics and vasodilators. Concurrently, non-oliguric acute renal failure developed, requiring haemodialysis. A renal biopsy showed typical features of thrombotic microangiopathy and massive deposition of mucin in the vessel walls (Figure 3). Blood pressure was finally controlled with the addition of an AT1-receptor-antagonist. Over the course of 3 weeks, a total of eight dialysis treatments were provided. Renal function recovered and creatinine decreased to 137 µmol/1, with bland urinary sediment.
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Impaired mental state, with disorientation and mental slowing which was apparent after occurrence of acute renal failure, posed another significant clinical problem. Therapy with four cycles of intravenous immunoglobulines in biweekly intervals (0.4 g/kg body weight per day on five consecutive days per cycle) was commenced, based on a recently published case of scleromyxedema with cerebral involvement [5]. Gradual improvement of her mental state and skin changes were observed. Pleural effusions decreased over time and were not detectable at discharge. Because of the difficulty in providing sufficient nutrition to the patient, temporary percutaneous tube feeding had to be initiated. Compared with the hypoproteinaemic state at admission, total protein was 73 g/l with 58% albumin at discharge.
The blood pressure continued to be controllable with a five-drug regimen, including an ACE-inhibitor and AT1-receptor-antagonist. On a follow-up exam 6 months later the serum creatinine had decreased to 116 µmol/1 and urinanalysis was unremarkable. Peripheral oedema and pleural effusions were absent and the skin indurations were much improved.
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Discussion |
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TopIntroductionCaseDiscussionReferences |
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Our case demonstrates classic cutaneous changes present in scleromyxedema. The skin changes began with photosensitivity years before the onset of swelling and skin induration, papules, and narrowing of the oral orifice. Skin histology confirmed the diagnosis. IgG kappa paraprotein was present in our case, which is common in scleromyxedema.
Renal manifestations in scleromyxedema appear to be rare. Reid et al. [6] reported a case with predominant and severe cerebral involvement, acute respiratory and renal failure. Hypertension was not reported. Post-mortem renal histology showed a necrotizing vasculitis without mucin deposits [6]. Gabriel et al. [1] described a case of progressive renal dysfunction over several months in a normotensive patient with Pneumocystis carinii pneumonia and respiratory failure. At autopsy, the kidneys were markedly swollen with diffuse petechial haemorrhage and showed vascular lesions in the interlobular and arcuate arteries, characteristic of scleroderma renal disease [1]. A third patient with an 8-month history of typical skin changes was reported [2], who initially presented with moderate hypertension and normal renal function. Fourteen months later, the patient developed uncontrolled hypertension and rapidly went into renal failure. A kidney biopsy showed concentric lamellar fibrosis of small arteries characteristic of scleroderma, and intimal proliferation with mural myxoid degeneration. After an acute psychotic phase, he became comatose, developed generalized seizures and died. Autopsy confirmed that the renal changes seen at biopsy and acid mucopolysaccharide deposits were demonstrated between intimal cells of smaller arteries. Other reports on renal involvement in scleromyxedema are listed in Table 1.
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In our patient, renal involvement had distinct similarities with scleroderma renal crisis. At the time of onset of hypertensive crisis, there was no evidence of pre-existing hypertension on echocardiography or ECG. Renal failure developed within 2 weeks and renal function recovered partially on an intensive therapy with an ACE-inhibitor and AT1-receptor antagonist, which are presumed to be efficacious in scleroderma renal crisis. To our knowledge, this is the first reported case of scleromyxedema and acute renal crisis, in which the patient survived with recovery of renal function, using a supportive haemodialysis treatment and blockade of the angiotensin system.
It is possible that scleromyxedema and scleroderma renal disease co-existed in our patient. The co-existence of dermal scleromyxedema, myositis and anti-Scl-70 auto-antibodies has been reported [7]. However, anti-Scl-70 or anti-centromer antibodies which are typically present in scleroderma were not found on repeated measurements in our patient. Renal biopsy showed severely narrowed pre-glomerular arteries, endothelial proliferation and microthromby, consistent with thrombotic microangiopathy. These findings were associated with a marked deposition of mucin in the vessel walls. We believe that these changes were not truly reflective of renal scleroderma. We suggest that scleromyxedema disease with vascular mucin deposition caused endothelial damage, leading to thrombotic microangiopathy. On the other hand, acute renal failure and hypertension may have been caused by the same pathophysiological mechanisms which are believed to be essential in scleroderma renal crisis [8], namely vasoconstriction of pre-glomerular arteries that have been altered by intimal proliferation, and activation of the renin-angiotensin aldosterone system.
Several other clinical features were present in our patient. Skin changes and the narrowing of the oral orifice were typical and responded well to steroid and immunoglobulins as reported by others [9]. It is unclear whether the patient's mental state changes were caused by hypertensive encephalopathy, ICU delirium or by scleromyxedema disease. Multiple neurological abnormalities have been reported in scleromyxedema [2,4,6,10–13]. Cerebral computed tomography or magnetic resonance imaging, as well as spinal fluid analysis, have been reported normal in such cases [5,6,9]. Autopsy studies either showed normal morphology or meningeal inflammation, vascular infarction and demyelinization, but deposition of mucin has not been observed [14]. The mental state of our patient normalized following therapy with steroid and immunoglobulins, which has been reported previously [5]. The pericardial and pleural effusions are rather unusual manifestations of scleromyxedema. In a series of 19 patients, only one patient had pericardial effusion [1]. Bilateral pleural effusions were reported in a patient with scleromyxedema, who died with pulmonary oedema and who had cardiac dilatation on autopsy [3]. Whether the effusions in our patient were related to the marked hypoproteinaemia or involvement of the viscera by scleromyxedema remains unresolved.
In summary, we presented a case with scleromyxedema with a scleroderma-like renal crisis, which was treated with supportive haemodialysis, an ACE-inhibitor and AT1-receptor antagonist, resulting in partial recovery of renal function.
Conflict of interest statement. None declared.
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References |
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- Gabriel SE, Perry HO, Oleson GB, Bowles CA. Scleromyxedema: a scleroderma-like disorder with systemic manifestations. Medicine (1988) 67:58–65.[Medline]
- Kantor GR, Bergfeld WF, Katzin WE, et al. Scleromyxedema associated with scleroderma renal disease and acute psychosis. J Am Acad Dermatol (1986) 14:879–888.[Web of Science][Medline]
- Donald GF, Hensley WJ, Mc GV. Lichen myxedematosus (papular mucinosis); a brief review of the literature and report of a case which failed to respond to ACTH and cortisone. Aust J Dermatol (1953) 2:28–34.[CrossRef][Medline]
- Farmer ER, Hambrick GW Jr, Shulman LE. Papular mucinosis. A clinicopathologic study of four patients. Arch Dermatol (1982) 118:9–13.
[Abstract/Free Full Text] - Shergill B, Orteu CH, McBride SR, Rustin MH. Dementia associated with scleromyxoedema reversed by high-dose intravenous immunoglobulin. Br J Dermatol (2005) 153:650–652.[CrossRef][Web of Science][Medline]
- Reid TL, Spoto DV, Larrabee GJ, Shlamowitz MA, Horowitz SA. Monoclonal paraproteinemia with subacute encephalopathy, seizures, and scleromyxedema. Neurology (1987) 37:1054–1057.
[Abstract/Free Full Text] - Bata-Csorgo Z, Husz S, Foldes M, et al. Scleromyxedema. J Am Acad Dermatol (1999) 41:343–346.[CrossRef][Web of Science][Medline]
- Donohoe JF. Scleroderma and the kidney. Kidney Int (1992) 41:462–477.[Web of Science][Medline]
- Lister RK, Jolles S, Whittaker S, et al. Scleromyxedema: response to high-dose intravenous immunoglobulin (hdIVIg). J Am Acad Dermatol (2000) 43:403–408.[Web of Science][Medline]
- Nieves DS, Bondi EE, Wallmark J, Raps EC, Seykora JT. Scleromyxedema: successful treatment of cutaneous and neurologic symptoms. Cutis (2000) 65:89–92.[Web of Science][Medline]
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- Webster GF, Matsuoka LY, Burchmore D. The association of potentially lethal neurologic syndromes with scleromyxedema (papular mucinosis). J Am Acad Dermatol (1993) 28:105–108.[Web of Science][Medline]
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Accepted in revised form: 7. 2.07
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